1. Field of the Invention
The present invention relates to novel ingestible polymeric phosphonium salts which are useful as sorbents for bile salts. More particularly, the invention is directed toward the treatment of hypercholesterolemia by removing through sorption the bile acids and salts from the small intestine, thereby increasing the catabolism of cholesterol in the liver with a concomitant decrease in the blood cholesterol level.
2. Description of the Background
All available evidence indicates that the incidence of higher than normal blood serum cholesterol levels in humans is associated with atherosclerosis and other hypercholesterolemic disease signs. Hypercholesterolemia, the leading cause of death in many countries, is presently treated by restricted and special dietary intake, inhibitation of cholesterol synthesis, accelerated catabolism and prevention of gastrointestinal adsorption, i.e., interruption of enterohepatic circulation. Increased catabolism of cholesterol can be achieved by the oral administration of bile salt binding agents.
Cholestyramine, the most widely used adsorbent for bile salts, is a copolymer of polystyrene and divinylbenzene with quaternary ammonium groups as functional groups. Being a typical strongly basic ion exchanger, its counterions of the quaternary ammonium, usually chloride ions, are exchanged with bile salt anions during the binding. The hydrophobic nature of the polymer backbone results in its poor biocompatibility. As a consequence, adverse side effects have been experienced by hypercholesterolemic patients. The drug has to be taken in large dosage and may cause stomach discomfort to patients.
Although widely used, non-absorbable sorbents such as the positively charged amine containing materials sold under the trade marks QUESTRAN and COLESTID have the setbacks of low adsorption capacity and undesirable side effects and are not completely satisfactory. Since hypercholesterolemia is a well recognized cause of cardiovascular disease, new and better drugs are urgently needed to replace the existing materials.
It is therefore an object of the present invention to overcome the above drawbacks and to provide novel bile salt sorbents with high sorption capacities, specificity and biocompatibility.